posted on 2022-12-28, 23:29authored byCarmanah Hunter, Zhizeng Gao, Hong-Ming Chen, Nicole Thompson, Warren Wakarchuk, Mark Nitz, Stephen G. Withers, Lisa M. Willis
Sialic acids are key mediators of
cell function, particularly
with
regard to cellular interactions with the surrounding environment.
Reagents that modulate the display of specific sialyl glycoforms at
the cell surface would be useful biochemical tools and potentially
allow for therapeutic intervention in numerous challenging chronic
diseases. While multiple strategies are being explored for the control
of cell surface sialosides, none that shows high selectivity between
sialyltransferases or that targets a specific sialyl glycoform has
yet to emerge. Here, we describe a strategy to block the formation
of α2,8-linked sialic acid chains (oligo- and polysialic acid)
through the use of 8-keto-sialic acid as a chain-terminating metabolic
inhibitor that, if incorporated, cannot be elongated. 8-Keto-sialic
acid is nontoxic at effective concentrations and serves to block polysialic
acid synthesis in cancer cell lines and primary immune cells, with
minimal effects on other sialyl glycoforms.